A method of making a sterile adhesive composition includes placing a mixture of a polymerizable adhesive monomer and a thickening agent in a container, sealing the container, and sterilizing the mixture and the container. The method provides superior viscosity for the monomer composition. An adhesive composition includes 2-octyl cyanoacrylate and at least one thickener. The sterile adhesive composition is particularly useful as a medical adhesive and can comprise 1,1-disubstituted ethylene monomers, such as xcex1-cyanoacrylates.

1. Field of the Invention
The invention relates to sterilized monomer and polymer adhesive and sealant compositions, and to their production for industrial and medical uses.
2. State of the Art
Monomer and polymer adhesives are used in both industrial (including household) and medical applications. Included among these adhesives are the 1,1-disubstituted ethylene monomers and polymers, such as the xcex1-cyanoacrylates. Since the discovery of the adhesive properties of such monomers and polymers, they have found wide use due to the speed with which they cure, the strength of the resulting bond formed, and their relative ease of use. These characteristics have made the xcex1-cyanoacrylate adhesives the primary choice for numerous applications such as bonding plastics, rubbers, glass, metals, wood, and, more recently, biological tissues.
It is known that monomeric forms of xcex1-cyanoacrylates are extremely reactive, polymerizing rapidly in the presence of even minute amounts of an initiator, including moisture present in the air or on moist surfaces such as animal tissue. Monomers of xcex1-cyanoacrylates are anionically polymerizable or free radical polymerizable, or polymerizable by zwitterions or ion pairs to form polymers. Once polymerization has been initiated, the cure rate can be very rapid.
Medical applications of 1,1-disubstituted ethylene adhesive compositions include use as an alternate and an adjunct to surgical sutures and staples in wound closure as well as for covering and protecting surface wounds such as lacerations, abrasions, burns, stomatitis, sores, and other open surface wounds. When an adhesive is applied to surfaces to be joined, it is usually applied in its monomeric form, and the resultant polymerization gives rise to the desired adhesive bond. However, at ordinary temperatures, the monomeric form runs when applied to surfaces. As a result, the monomeric adhesive may spread into a wound or along a surface to areas that do not require an adhesive. Therefore, the monomeric form must be controlled in order to prevent undue escape of the adhesive from any given area to which the adhesive is applied. Additionally, sufficient time must be allowed for the monomeric material to polymerize and thus to bring about the desired bonding action. In order to achieve a suitably viscous adhesive, thickening agents can be added to the monomer compositions.
For example, U.S. Pat. No. 3,527,841 to Wicker et al. discloses xcex1-cyanoacrylate adhesive compositions for both general and surgical uses containing a viscosity modifier that is soluble, after heating, in a wide range of the esters of xcex1-cyanoacrylic acid. The viscosity modifier is disclosed as poly(lactic acid). After addition of the poly(lactic acid), the composition is sterilized at temperatures up to 150xc2x0 C. Most of the resulting compositions experienced a decrease in viscosity, presumably resulting from degradation of the thickener by the sterilization process.
U.S. Pat. No. 5,665,817 to Greff et al. discloses alkyl cyanoacrylate compositions suitable for topical application to human skin. The compositions may comprise a suitable amount of a thickening agent to provide a compositional viscosity suitable for certain applications onto human skin. The thickening agent is added to provide a viscosity of from about 2 to 50,000 centipoise at 20xc2x0 C. The thickening agent employed is any biocompatible material that increases the viscosity of the alkyl cyanoacrylate composition and includes, by way of example, a partial polymer of the alkyl cyanoacrylate, polymethylmethacrylate (PMMA), or other preformed polymers soluble in the alkyl cyanoacrylate. When these solutions are to be stored in applicators suitable for repeated intermittent use, the alkyl cyanoacrylate composition is stored at ambient conditions and is selected to be bacteriostatic. When the selected composition is bacteriostatic, prolonged storage at ambient conditions is without regard to the sterility of the formulation because there is no adverse buildup of bacteria during storage.
U.S. Pat. No. 5,328,687 to Leung et al. also discloses adhesive compositions that may be used for bonding tissue. Compositions comprising xcex1-cyanoacrylate monomers are preferred. The compositions may further contain adjuvant substances such as thickening agents. Suitable disclosed thickeners include, for example, polycyanoacrylates, polylactic acid, polyglycolic acid, lactic-glycolic acid copolymers, polycaprolactone, lactic acid-caprolactone copolymers, poly-3-hydroxybutyric acid, polyorthoesters, polyalkyl acrylates, copolymers of alkylacrylate and vinyl acetate, polyalkyl methacrylates, and copolymers of alkyl methacrylates and butadiene. Without specific reference to thickened or unthickened compositions, the ""687 patent also mentions that compositions employed in the invention are sterilizable by conventional methods such as by autoclave or by aseptic filtration techniques.
In addition to being viscous, cyanoacrylate compositions for use in many medical applications should be sterile. Due to the importance of achieving and maintaining sterility of these compositions, when an additive, such as a thickening agent, is added to an xcex1-cyanoacrylate composition, it should be added prior to sterilization. A problem arises because some thickeners require pretreatment prior to addition to the monomer compositions. U.S. Pat. No. 4,038,345 to O""Sullivan et al. discloses stable cyanoacrylate adhesive compositions having viscosities greater than about 200 centipoise. The compositions are prepared by incorporating, as a thickening agent, a soluble acrylic polymer having a reduced viscosity of about 5 or greater, and a content of free radical polymerization initiator less than 1% by weight. These properties are obtained by subjecting the thickening agent to temperatures of about 140-180xc2x0 C. for about 30-180 minutes prior to incorporating it in the cyanoacrylate. In one aspect, the ""345 patent concerns a process for preparing improved cyanoacrylates which involves heating a conventional polyacrylate thickener at a suitable temperature and for a suitable period of time to reduce its content of free radical polymerization initiators to below about one percent, and increase its reduced viscosity to greater than 5; and dissolving a sufficient amount of the thickener in an ester of 2-cyanoacrylic acid to produce a cyanoacrylate adhesive composition having a viscosity of at least about 500 centipoise. The most highly preferred thickening compound is poly(methylmethacrylate). This thickener is incorporated into the cyanoacrylate monomer by stirring to form a solution. In preparing the thickener, it is maintained at an elevated temperature for a suitable period of time. A satisfactory temperature range is between about 140xc2x0 and 180xc2x0 C., and a satisfactory time period is from about 30 to 180 minutes.
However, regardless of the type and number of additives, sterilization of xcex1-cyanoacrylate adhesive compositions is often difficult to achieve. For example, widely practiced methods of sterilization, such as dry and moist heat sterilization, ionizing radiation, exposure to gas, and sterile filtration, are often not suitable for use with monomeric cyanoacrylate compositions. Problems arise due to polymerization of the monomer during the sterilization process. In many cases, sterilization-induced polymerization is so severe that the resulting product is unusable.
Methods currently used to package and sterilize xcex1-cyanoacrylate monomer compositions have been developed with the recognition that, to improve efficiency and productivity, the packaging and sterilizing steps should be performed in rapid succession. However, these methods do not provide the desired viscosity of the adhesive compositions. For example, U.S. Pat. No. 5,530,037 to McDonnell et al. discloses that the composition of a sterilized adhesive would be very limited because necessary additives could not be conveniently added and mixed in a controlled fashion. For example, viscosity modifiers such as polymethylmethacrylate (PMMA) would require heating in a separate vessel to achieve dissolution and this step would destroy the sterility.
Additionally, the problem exists that some thickeners decompose in electron beam and dry heat sterilization. One example of this is poly(2-octylcyanoacrylate), which degrades when exposed to a 160xc2x0 C. dry heat sterilization cycle or 20-30 kGy of electron beam radiation. In order to confirm this, formulations were prepared using poly(2-octylcyanacrylate), as a thickening agent and 2-octylcyanoacetate as the non-polymerizable medium. The data in Table I confirms that poly(2-octylcyanoacrylate) is unstable under current dry heat and electron beam sterilization methods.
Viscosity is used as a measure of stability since a stable formulation should have a viscosity change of zero after sterilization. If the viscosity decreases, this indicates degradation of the thickener (here, poly(2-octylcyanoacrylate)).
Many other thickeners are also subject to decomposition under sterilization conditions. Such instability is particularly common in compositions in which the adhesive monomers are stabilized by the presence of acids, because those acids frequently destabilize the thickening polymers also present in the composition. For example, lactic acid-caprolactone copolymers in a stabilized 2-octylcyanoacrylate monomer composition tend to decompose when such a composition is subjected to dry heat sterilization conditions, causing the thickener to lose thickening effect. Such acid stabilizers are, however, present in many cyanoacrylate adhesive compositions.
In addition, aseptic filtration is a known method for sterilizing cyanoacrylate compositions before they are placed into a container. However, aseptic filtration is very difficult with high viscosity compositions, and involves prohibitively expensive technology.
Thus, a need exists for improved monomer cyanoacrylate adhesive compositions, especially for medical uses, having a greater viscosity without sacrificing the performance of the adhesive. The need further exists for a sterilized monomeric adhesive composition that does not require pre-treatment of the thickener prior to its addition to the monomeric adhesive. Additionally, the need exists for a sterilized monomeric adhesive in which the thickener has not decomposed during sterilization.
The present invention provides a method of making a thickened sterile monomeric adhesive composition. Production of the composition includes placing a mixture of a polymerizable 1,1-disubstituted ethylene monomer and a thickening agent in a container, sealing the container and sterilizing the container and the mixture. The thickening agent is soluble in the monomer at room temperature. The compositions produced, packaged and sterilized according to the present invention have greater viscosity, and extended utility, as compared to adhesive compositions of the prior art.
According to the invention, a sterile viscous monomeric adhesive composition is manufactured by adding a thickening agent to a composition comprising a monomer adhesive prior to sterilization.
The thickening agents may be selected from among known thickeners, including, but not limited to, poly(2-ethylhexyl methacrylate), poly(2-ethylhexyl acrylate) and cellulose acetate butyrate. Suitable thickeners include, for example, polycyanoacrylates, polyoxalates, lactic-glycolic acid copolymers, polycaprolactone, lactic acid-caprolactone copolymers, poly(caporolactone+DL-lactide+glycolide), polyorthoesters, polyalkyl acrylates, copolymers of alkylacrylate and vinyl acetate, polyalkyl methacrylates, and copolymers of alkyl methacrylates and butadiene. Examples of alkyl methacrylates and acrylates are poly(butylmethacrylate) and poly(butylacrylate), also copolymers of various acrylate and methacrylate monomers, such as poly(butylmethacrylate-co-methylmethacrylate). Biodegradable polymer thickeners are preferred for some uses such as some surgical uses. Preferably, the thickening agent is soluble in a monomer composition at room temperature (i.e., 20-25xc2x0 C.) so that it may be added to the monomer composition without excessive heating of the monomer composition and remain uniformly combined in the composition.
The amount of thickening agent that is added to the monomer composition depends upon the molecular weight of the thickening agent. The thickening agent preferably comprises from about 0.5-25.0% by weight of the adhesive composition. In preferred embodiments, the thickening agent comprises from about 1.0-10.0%, more preferably 1.0-5.0%, of the adhesive composition. In embodiments, the thickening agent has a high molecular weight, preferably at least 100,000, or at least 500,000 or at least 1,000,000. The thickening agent is selected such that it is compatible with the monomer (i.e., does not adversely affect polymerization, bond strength, core properties, or shelf-life). The amount of thickening agent to be used can be determined by one of ordinary skill in the art using known techniques without undue experimentation.
In embodiments, the sterilized adhesive composition has a viscosity of about 20-500 centipoise, preferably 30-400 centipoise, as measured with a Brookfield Viscometer at 25xc2x0 C. Additionally, the viscosity of the composition should be maintained or increased by a controlled and acceptable amount after sterilization.
According to embodiments of the present invention, the stability, and thus the shelf-life, of some monomeric adhesive compositions can be further enhanced and extended through careful regulation of the packaging (i.e., dispensing into a container) and sterilizing procedures. In preferred embodiments, there is substantially no initiation of polymerization of monomeric liquid adhesive compositions that affects the utility of the monomer or monomers caused by the sterilization process. In particular, a polymerizable 1,1-disubstituted monomer and a thickening agent are dispensed into a container. The container is sealed and subjected to sterilization.
The monomeric composition may be packaged in any type of suitable container fabricated from materials including, but not limited to, glass, plastic, metal packages, and film-formed packages. Suitable containers are those into which the compositions can be dispensed and sterilized without unacceptable damage to, or degradation of, the container or the components of the monomer composition. Glass is especially preferred when sterilization is achieved with dry heat because of the lack of stability of many plastics at the temperatures used for dry heat sterilization (typically at least 160xc2x0 C.). Examples of types of containers include, but are not limited to, ampoules, vials, syringes, pipettes, and the like. In a preferred embodiment, the container comprises a sealable container.
In embodiments, monomer compositions according to the invention are sterilized. The sterilization can be accomplished by techniques known to the skilled artisan, and is preferably accomplished by methods including, but not limited to, chemical, physical, and irradiation methods. Examples of chemical methods include, but are not limited to, exposure to ethylene oxide or hydrogen peroxide vapor. Examples of physical methods include, but are not limited to, sterilization by heat (dry or moist). Examples of irradiation methods include, but are not limited to, gamma irradiation, electron beam irradiation, and microwave irradiation. Preferred methods are dry and moist heat sterilization and electron beam sterilization. In embodiments where a composition is to be used for medical applications, the sterilized composition must show low levels of toxicity to living tissue during its useable life.
The sterilization conditions and thickeners should be selected in light of each other, and preferably also in light of other components of the composition. For example, in a highly acid stabilized composition, a less acid-unstable thickener and/or less degrading sterilization conditions would be preferable. Biodegradable polymer thickeners such as lactic acid-caprolactone copolymers, for example, better survive electron beam sterilization rather than dry heat sterilization in acid stabilized cyanoacrylate compositions. Where a biodegradable thickener is not required, on the other hand, a more acid-stable thickener such as poly(2-ethylhexyl) methacrylate may be used with, for example, dry heat sterilization. Thus, by taking into account the selection of the thickener and the selection of the sterilization conditions, along with the nature of the underlying composition, one of ordinary skill in the art can readily select appropriate parameters by routine experimentation to allow sterilization of a thickened adhesive composition in a container.
The monomer composition, in embodiments, is preferably a monomeric (including prepolymeric) adhesive composition. The monomer composition may further include one or more polymerizable monomers. In embodiments, at least one of the one or more monomers is a 1,1-disubstituted ethylene monomer, e.g., an xcex1-cyanoacrylate. Preferred monomer compositions of the present invention, and polymers formed therefrom, are useful as tissue adhesives, sealants for preventing bleeding or for covering open wounds, and in other biomedical applications. They find uses in, for example, apposing surgically incised or traumatically lacerated tissues; retarding blood flow from wounds; drug delivery; dressing burns; dressing skin or other superficial or surface wounds (such as abrasions, chaffed or raw skin, and/or stomatitis); and aiding repair and regrowth of living tissue. Other preferred monomer compositions of the present invention, and polymers formed therefrom, are useful in industrial and home applications, for example in bonding rubbers, plastics, wood, composites, fabrics, and other natural and synthetic materials.
Monomers that may be used in this invention are readily polymerizable, e.g. anionically polymerizable or free radical polymerizable, or polymerizable by zwitterions or ion pairs to form polymers. Such monomers include those that form polymers, that may, but do not need to, biodegrade. Such monomers are disclosed in, for example, U.S. Pat. No. 5,328,687 to Leung, et al., which is hereby incorporated in its entirety by reference herein.
Useful 1,1-disubstituted ethylene monomers include, but are not limited to, monomers of the formula:
HRCxe2x95x90CXYxe2x80x83xe2x80x83(I)
wherein X and Y are each strong electron withdrawing groups, and R is H, xe2x80x94CHxe2x95x90CH2 or, provided that X and Y are both cyano groups, a C1-C4 alkyl group.
Examples of monomers within the scope of formula (I) include xcex1-cyanoacrylates, vinylidene cyanides, C1-C4 alkyl homologues of vinylidene cyanides, dialkyl methylene malonates, acylacrylonitriles, vinyl sulfinates and vinyl sulfonates of the formula CH2xe2x95x90CXxe2x80x2Yxe2x80x2 wherein Xxe2x80x2 is xe2x80x94SO2Rxe2x80x2 or xe2x80x94SO3Rxe2x80x2 and Yxe2x80x2 is xe2x80x94CN, xe2x80x94COORxe2x80x2, xe2x80x94COCH3, xe2x80x94SO2Rxe2x80x2 or xe2x80x94SO3Rxe2x80x2, and Rxe2x80x2 is H or hydrocarbyl.
Preferred monomers of formula (I) for use in this invention are xcex1-cyanoacrylates. These monomers are known in the art and have the formula
wherein R2 is hydrogen and R3 is a hydrocarbyl or substituted hydrocarbyl group; a group having the formula xe2x80x94R4xe2x80x94Oxe2x80x94R5xe2x80x94Oxe2x80x94R6, wherein R4 is a 1,2-alkylene group having 2-4 carbon atoms, R5 is an alkylene group having 2-4 carbon atoms, and R6 is an alkyl group having 1-6 carbon atoms; or a group having the formula
wherein R7 is
wherein n is 1-10, preferably 1-5 carbon atoms and R8 is an organic moiety.
Examples of suitable hydrocarbyl and substituted hydrocarbyl groups include straight chain or branched chain alkyl groups having 1-16 carbon atoms; straight chain or branched chain C1-C16 alkyl groups substituted with an acyloxy group, a haloalkyl group, an alkoxy group, a halogen atom, a cyano group, or a haloalkyl group; straight chain or branched chain alkenyl groups having 2 to 16 carbon atoms; straight chain or branched chain alkynyl groups having 2 to 12 carbon atoms; cycloalkyl groups; aralkyl groups; alkylaryl groups; and aryl groups.
The organic moiety R8 may be substituted or unsubstituted and may be straight chain, branched or cyclic, saturated, unsaturated or aromatic. Examples of such organic moieties include C1-C8 alkyl moieties, C2-C8 alkenyl moieties, C2-C8 alkynyl moieties, C3-C12 cycloaliphatic moieties, aryl moieties such as phenyl and substituted phenyl and aralkyl moieties such as benzyl, methylbenzyl, and phenylethyl. Other organic moieties include substituted hydrocarbon moieties, such as halo (e.g., chloro-, fluoro- and bromo-substituted hydrocarbons) and oxy-substituted hydrocarbon (e.g., alkoxy substituted hydrocarbons) moieties. Preferred organic radicals are alkyl, alkenyl, and alkynyl moieties having from 1 to about 8 carbon atoms, and halo-substituted derivatives thereof. Particularly preferred are alkyl moieties of 4 to 6 carbon atoms.
In the cyanoacrylate monomer of formula (II), R3 is preferably an alkyl group having 1-10 carbon atoms or a group having the formula xe2x80x94AOR9, wherein A is a divalent straight or branched chain alkylene or oxyalkylene moiety having 2-8 carbon atoms, and R9 is a straight or branched alkyl moiety having 1-8 carbon atoms.
Examples of groups represented by the formula xe2x80x94AOR9 include 1-methoxy-2-propyl, 2-butoxy ethyl, isopropoxy ethyl, 2-methoxy ethyl, and 2-ethoxy ethyl.
The xcex1-cyanoacrylates of formula (II) can be prepared according to methods known in the art. U.S. Pat. Nos. 2,721,858 and 3,254,111, each of which is hereby incorporated in its entirety by reference, disclose methods for preparing xcex1-cyanoacrylates. For example, the xcex1-cyanoacrylates can be prepared by reacting an alkyl cyanoacetate with formaldehyde in a non-aqueous organic solvent and in the presence of a basic catalyst, followed by pyrolysis of the anhydrous intermediate polymer in the presence of a polymerization inhibitor. The xcex1-cyanoacrylate monomers prepared with low moisture content and essentially free of impurities are preferred for biomedical use.
The xcex1-cyanoacrylates of formula (II) wherein R3 is a group having the formula R4xe2x80x94Oxe2x80x94R5xe2x80x94Oxe2x80x94R6 can be prepared according to the method disclosed in U.S. Pat. No. 4,364,876 to Kimura et al., which is hereby incorporated in its entirety by reference. In the Kimura et al. method, the xcex1-cyanoacrylates are prepared by producing a cyanoacetate by esterifying cyanoacetic acid with an alcohol or by transesterifying an alkyl cyanoacetate and an alcohol; condensing the cyanoacetate and formaldehyde or para-formaldehyde in the presence of a catalyst at a molar ratio of 0.5-1.5:1, preferably 0.8-1.2:1, to obtain a condensate; depolymerizing the condensation reaction mixture either directly or after removal of the condensation catalyst to yield crude cyanoacrylate; and distilling the crude cyanoacrylate to form a high purity cyanoacrylate.
The xcex1-cyanoacrylates of formula (II) wherein R3 is a group having the formula
can be prepared according to the procedure described in U.S. Pat. No. 3,995,641 to Kronenthal et al., which is hereby incorporated in its entirety by reference. In the Kronenthal et al. method, such xcex1-cyanoacrylate monomers are prepared by reacting an alkyl ester of an xcex1-cyanoacrylic acid with a cyclic 1,3-diene to form a Diels-Alder adduct which is then subjected to alkaline hydrolysis followed by acidification to form the corresponding xcex1-cyanoacrylic acid adduct. The xcex1-cyanoacrylic acid adduct is preferably esterified by an alkyl bromoacetate to yield the corresponding carbalkoxymethyl xcex1-cyanoacrylate adduct. Alternatively, the xcex1-cyanoacrylic acid adduct may be converted to the xcex1-cyanoacrylyl halide adduct by reaction with thionyl chloride. The xcex1-cyanoacrylyl halide adduct is then reacted with an alkyl hydroxyacetate or a methyl substituted alkyl hydroxyacetate to yield the corresponding carbalkoxymethyl xcex1-cyanoacrylate adduct or carbalkoxy alkyl xcex1-cyanoacrylate adduct, respectively. The cyclic 1,3-diene blocking group is finally removed and the carbalkoxy methyl xcex1-cyanoacrylate adduct or the carbalkoxy alkyl xcex1-cyanoacrylate adduct is converted into the corresponding carbalkoxy alkyl xcex1-cyanoacrylate by heating the adduct in the presence of a slight deficit of maleic anhydride.
Examples of monomers of formula (II) include cyanopentadienoates and xcex1-cyanoacrylic of the formula:
wherein Z is xe2x80x94CHxe2x95x90CH2 and R3 is as defined above. The monomers of formula (III) wherein R3 is an alkyl group of 1-10 carbon atoms, i.e., the 2-cyanopenta-2,4-dienoic acid esters, can be prepared by reacting an appropriate 2-cyanoacetate with acrolein in the presence of a catalyst such as zinc chloride. This method of preparing 2-cyanopenta-2,4-dienoic acid esters is disclosed, for example, in U.S. Pat. No. 3,554,990, which is hereby incorporated in its entirety by reference.
Preferred xcex1-cyanoacrylate monomers used in this invention are alkyl xcex1-cyanoacrylates including octyl cyanoacrylate, such as 2-octyl cyanoacrylate; dodecyl cyanoacrylate; 2-ethylhexyl cyanoacrylate; butyl cyanoacrylate such as n-butyl cyanoacrylate; ethyl cyanoacrylate; methyl cyanoacrylate; 3-methoxybutyl cyanoacrylate; 2-butoxyethyl cyanoacrylate; 2-isopropoxyethyl cyanoacrylate; and 1-methoxy-2-propyl cyanoacrylate. More preferred monomers are n-butyl and 2-octyl xcex1-cyanoacrylate. Monomers utilized for medical purposes in the present application should be very pure and contain few impurities (e.g., surgical grade). Monomers utilized for industrial purposes need not be as pure.
The composition may optionally also include at least one plasticizing agent that imparts flexibility to the polymer formed from the monomer. The plasticizing agent preferably contains little or no moisture and should not significantly affect the stability or polymerization of the monomer. Such plasticizers are useful in polymerized compositions to be used for closure or covering of wounds, incisions, abrasions, sores or other applications where flexibility of the adhesive is desirable. Some thickeners, such as poly-2-ethylhexylcyanoacrylate, can also impart flexibility to the polymer.
Examples of suitable plasticizers include acetyl tributyl citrate, dimethyl sebacate, triethyl phosphate, tri(2-ethylhexyl)phosphate, tri(p-cresyl) phosphate, glyceryl triacetate, glyceryl tributyrate, diethyl sebacate, dioctyl adipate, isopropyl myristate, butyl stearate, lauric acid, trioctyl trimellitate, dioctyl glutarate, and mixtures thereof. Preferred plasticizers are tributyl citrate and acetyl tributyl citrate. In embodiments, suitable plasticizers include polymeric plasticizers, such as polyethylene glycol (PEG) esters and capped PEG esters or ethers, polyester glutarates and polyester adipates.
The addition of plasticizing agents in amounts ranging from about 0.5 wt. % to about 25 wt. %, or from about 1 wt. % to about 20 wt. %, or from about 3 wt. % to about 15 wt. % or from about 5 wt. % to about 7 wt. % provides increased elongation and toughness of the polymerized monomer over polymerized monomers not having plasticizing agents.
The composition may also optionally include at least one thixotropic agent. Suitable thixotropic agents are known to the skilled artisan and include, but are not limited to, silica gels such as those treated with a silyl isocyanate. Examples of suitable thixotropic agents are disclosed in, for example, U.S. Pat. No. 4,720,513, the disclosure of which is hereby incorporated in its entirety.
The composition may also optionally include at least one natural or synthetic rubber to impart impact resistance, which is preferable especially for industrial compositions of the present invention. Suitable rubbers are known to the skilled artisan. Such rubbers include, but are not limited to, dienes, styrenes, acrylonitriles, and mixtures thereof. Examples of suitable rubbers are disclosed in, for example, U.S. Pat. Nos. 4,313,865 and 4,560,723, the disclosures of which are hereby incorporated in their entireties.
The composition may also optionally include both at least one anionic vapor phase stabilizer and at least one anionic liquid phase stabilizer. These stabilizing agents inhibit polymerization. Such stabilizing agents may also include mixtures of anionic stabilizing agents and radical stabilizing agents. Any mixture of stabilizers is included as long as the mixture does not inhibit the desired polymerization of the monomer and is compatible with the selected thickener under the selected sterilization conditions, as discussed above.
The anionic vapor phase stabilizers may be selected from among known stabilizers, including, but not limited to, sulfur dioxide, boron trifluoride, and hydrogen fluoride. The amount of anionic vapor phase stabilizer that is added to the monomer composition depends on the identity of the liquid phase stabilizer(s) chosen in combination with it, the monomer to be stabilized, as well as the packaging material to be used for the composition. Preferably, each anionic vapor phase stabilizer is added to give a concentration of less than 200 parts per million (ppm). In preferred embodiments, each anionic vapor phase stabilizer is present from about 1 to 200 ppm, more preferably from about 10 to 75 ppm, even more preferably from about 10 to 50 ppm, and most preferably from 10 to 20 ppm. The amount to be used can be determined by one of ordinary skill in the art using known techniques without undue experimentation.
In embodiments, the vapor phase comprises, among other things, an anionic stabilizer that is sulfur dioxide. In embodiments, the vapor phase comprises, among other things, a stabilizer that is boron trifluoride or hydrogen fluoride. A combination of sulfur dioxide and boron trifluoride or hydrogen fluoride is preferable in some embodiments.
In embodiments, the liquid phase anionic stabilizer is a very strong acid. As used herein, a very strong acid is an acid that has an aqueous pKa of less than 1.0. Suitable very strong acidic stabilizing agents include, but are not limited to, very strong mineral and/or oxygenated acids. Examples of such very strong acids include, but are not limited to, sulfuric acid (pKa xe2x88x923.0), perchloric acid (pKa xe2x88x925), hydrochloric acid (pKa xe2x88x927.0), hydrobromic acid (pKa xe2x88x929), fluorosulfonic acid (pKa  less than xe2x88x9210), chlorosulfonic acid (pKa xe2x88x9210). In embodiments, the very strong acid liquid phase anionic stabilizer is added to give a final concentration of 1 to 200 ppm. Preferably, the very strong acid liquid phase anionic stabilizer is present in a concentration of from about 5 to 80 ppm, more preferably 10 to 40 ppm. The amount of very strong acid liquid phase anionic stabilizer to be used can be determined by one of ordinary skill in the art without undue experimentation.
Preferably, the very strong acid liquid phase anionic stabilizer is sulfuric acid, perchloric acid, or chlorosulfonic acid. More preferably, the very strong acid liquid phase anionic stabilizer is sulfuric acid.
In embodiments, sulfur dioxide is used as a vapor phase anionic stabilizer and sulfuric acid is used as a liquid phase anionic stabilizer.
The composition may also optionally include at least one other anionic stabilizing agent that inhibits polymerization. These agents are herein referred to as secondary anionic active agents to contrast them with the strong or very strong liquid phase anionic stabilizers, which are referred to hereinbelow as xe2x80x9cprimaryxe2x80x9d anionic stabilizers. The secondary anionic active agents can be included in the compositions to adjust the cure speed of the adhesive composition, for example.
The secondary anionic active agent would normally be an acid with a higher pKa than the primary anionic stabilizing agent and may be provided to more precisely control the cure speed and stability of the adhesive, as well as the molecular weight of the cured adhesive. Any mixture of primary anionic stabilizers and secondary active agents is included as long as the chemistry of the composition is not compromised and the mixture does not significantly inhibit the desired polymerization of the composition. Furthermore, the mixture should not, in medical adhesive compositions, show unacceptable levels of toxicity.
Suitable secondary anionic active agents include those having aqueous pKa ionization constants ranging from 2 to 8, preferably from 2 to 6, and most preferably from 2 to 5. Examples of such suitable secondary anionic stabilizing agents include, but are not limited to, phosphoric acid (pKa 2.2), organic acids, such as acetic acid (pKa 4.8), benzoic acid (pKa 4.2), chloroacetic acid (pKa 2.9), cyanoacetic acid, and mixtures thereof. Preferably these secondary anionic stabilizing agents are organic acids, such as acetic acid or benzoic acid. In embodiments, the amount of acetic acid and/or benzoic acid is about 25-500 ppm. The concentration of acetic acid is typically 50-400 ppm, preferably 75-300 ppm, and more preferably 100-200 ppm. When using a stronger acid such as phosphoric acid, a concentration of 20-100 ppm, preferably 30-80 ppm, and more preferably 40-60 ppm may be utilized.
Combinations of at least one vapor phase stabilizer and at least one liquid phase anionic stabilizer are preferred. For example, combinations of sulfur dioxide and sulfuric acid, sulfur dioxide and perchloric acid, sulfur dioxide and chlorosulfonic acid, boron trifluoride and sulfuric acid, boron trifluoride and perchloric acid, boron trifluoride and chlorosulfonic acid, boron trifluoride and methanesulfonic acid, hydrogen fluoride and sulfuric acid, hydrogen fluoride and perchloric acid, hydrogen fluoride and chlorosulfonic acid, and hydrogen fluoride and methanesulfonic acid can be used. A combination of boron trifluoride, sulfur dioxide, and sulfuric acid can also be used, among other combinations. The two types of anionic stabilizers are chosen in conjunction such that the stabilizers are compatible with the chosen adhesive composition and each other stabilizer, as well as with the packaging material and the equipment used to make and package the composition. In other words, the combination of vapor phase stabilizer(s), liquid phase stabilizer(s), and monomer should be such that a stabilized, substantially unpolymerized adhesive composition is present after packaging.
Medical compositions of the present invention may also include at least one biocompatible agent effective to reduce active formaldehyde concentration levels produced during in vivo biodegradation of the polymer (also referred to herein as xe2x80x9cformaldehyde concentration reducing agentsxe2x80x9d). Preferably, this component is a formaldehyde scavenger compound. Examples of formaldehyde scavenger compounds useful in this invention include sulfites; bisulfites; mixtures of sulfites and bisulfites; ammonium sulfite salts; amines; amides; imides; nitriles; carbamates; alcohols; mercaptans; proteins; mixtures of amines, amides, and proteins; active methylene compounds such as cyclic ketones and compounds having a b-dicarbonyl group; and heterocyclic ring compounds free of a carbonyl group and containing an NH group, with the ring made up of nitrogen or carbon atoms, the ring being unsaturated or, when fused to a phenyl group, being unsaturated or saturated, and the NH group being bonded to a carbon or a nitrogen atom, which atom is directly bonded by a double bond to another carbon or nitrogen atom.
Bisulfites and sulfites useful as the formaldehyde scavenger compound in this invention include alkali metal salts such as lithium, sodium, and potassium salts, and ammonium salts, for example, sodium bisulfite, potassium bisulfite, lithium bisulfite, ammonium bisulfite, sodium sulfite, potassium sulfite, lithium sulfite, ammonium sulfite, and the like.
Examples of amines useful in this invention include the aliphatic and aromatic amines such as, for example, aniline, benzidine, aminopyriridine, toluene-diamine, triethylenediamine, diphenylamine, diaminodiphenylamine, hydrazines, and hydrazide.
Suitable proteins include collagen, gelatin, casein, soybean protein, vegetable protein, keratin, and glue. The preferred protein for use in this invention is casein.
Suitable amides for use in this invention include urea, cyanamide, acrylamide, benzamide, and acetamide. Urea is a preferred amide.
Suitable alcohols include phenols, 1,4-butanediol, d-sorbitol, and polyvinyl alcohol.
Examples of suitable compounds having a b-dicarbonyl group include malonic acid, acetylacetone, ethylacetone, acetate, malonamide, diethylmalonate, or another malonic ester.
Preferred cyclic ketones for use in this invention include cyclohexanone or cyclopentanone.
Examples of suitable heterocyclic compounds for use as the formaldehyde scavenger in this invention are disclosed, for example, in U.S. Pat. No. 4,127,382 to Perry, which is hereby incorporated in its entirety by reference. Such heterocyclic compounds include, for example, benzimidazole, 5-methyl benzimidazole, 2-methylbenzimidazole, indole, pyrrole, 1,2,4-triazole, indoline, benzotriazole, indoline, and the like.
A preferred formaldehyde scavenger for use in this invention is sodium bisulfite.
In practicing the present invention, the formaldehyde concentration reducing agent is added in an effective amount to the cyanoacrylate. The xe2x80x9ceffective amountxe2x80x9d is that amount sufficient to reduce the amount of formaldehyde generated during subsequent in vivo biodegradation of the polymerized cyanoacrylate. This amount will depend on the type of active formaldehyde concentration reducing agent, and can be readily determined without undue experimentation by those skilled in the art.
The formaldehyde concentration reducing agent may be used in this invention in either free form or in microencapsulated form. When microencapsulated, the formaldehyde concentration reducing agent is released from the microcapsule continuously over a period of time during the in vivo biodegradation of the cyanoacrylate polymer.
For purposes of this invention, the microencapsulated form of the formaldehyde concentration reducing agent is preferred because this embodiment prevents or substantially reduces polymerization of the cyanoacrylate monomer by the formaldehyde concentration reducing agent, which increases shelf-life and facilitates handling of the monomer composition during use.
Microencapsulation of the formaldehyde scavenger can be achieved by many known microencapsulation techniques. For example, microencapsulation can be carried out by dissolving a coating polymer in a volatile solvent, e.g., methylene chloride, to a polymer concentration of about 6% by weight; adding a formaldehyde scavenger compound in particulate form to the coating polymer/solvent solution under agitation to yield a scavenger concentration of 18% by weight; slowly adding a surfactant-containing mineral oil solution to the polymer solution under rapid agitation; allowing the volatile solvent to evaporate under agitation; removing the agitator; separating the solids from the mineral oil; and washing and drying the microparticles. The size of the microparticles will range from about 0.001 to about 1000 microns.
The coating polymer for microencapsulating the formaldehyde concentration reducing agent should be polymers which undergo in vivo bioerosion, preferably at rates similar to or greater than the cyanoacrylate polymer formed by the monomer, and should have low inherent moisture content. Such bioerosion can occur as a result of the physical or chemical breakdown of the encapsulating material, for example, by the encapsulating material passing from solid to solute in the presence of body fluids, or by biodegradation of the encapsulating material by agents present in the body.
Examples of coating materials which can be used to microencapsulate the formaldehyde concentration reducing agent include polyesters, such as polyglycolic acid, polylactic acid, poly-1,4-dioxa-2-one, polyoxaltes, polycarbonates, copolymers of polyglycolic acid and polylactic acid, polycaprolactone, poly-b-hydroxybutyrate, copolymers of epsilon-caprolactone and delta-valerolactone, copolymers of epsilon-caprolactone and DL-dilactide, and polyester hydrogels; polyvinylpyrrolidone; polyamides; gelatin; albumin; proteins; collagen; poly(orthoesters); poly(anhydrides); poly(alkyl-2-cyanoacrylates); poly(dihydropyrans); poly(acetals); poly(phosphazenes); poly(urethanes); poly(dioxinones); cellulose; and starches.
Examples of surfactants which can be added to the mineral oil include those commercially available under the designations Triton X-100(trademark) (Rohm and Haas) (octoxynol), Tween 20(trademark) (ICI Americas) (polysorbate), and Tween 80(trademark) (ICI Americas) (polysorbate).
To improve the cohesive strength of adhesives formed from the compositions of this invention, difunctional monomeric cross-linking agents may be added to the monomer compositions of this invention. Such crosslinking agents are known. U.S. Pat. No. 3,940,362 to Overhults, which is hereby incorporated in its entirety by reference, discloses such cross-linking agents. Examples of suitable crosslinking agents include alkyl bis(2-cyanoacrylates), triallyl isocyanurates, alkylene diacrylates, alkylene dimethacrylates, trimethylol propane triacrylate, and alkyl bis(2-cyanoacrylates). A catalytic amount of an amine activated free radical initiator or rate modifier may be added to initiate polymerization or to modify the rate of polymerization of the cyanoacrylate monomer/crosslinking agent blend.
The compositions of this invention may further contain fibrous reinforcement and colorants such as dyes, pigments, and pigment dyes. Examples of suitable fibrous reinforcement include PGA microfibrils, collagen microfibrils, cellulosic microfibrils, and olefinic microfibrils. Examples of suitable colorants include 1-hydroxy-4-[4-methylphenyl-amino]-9,10 anthracenedione (D+C violet No. 2); disodium salt of 6-hydroxy-5-[(4-sulfophenyl)axo]-2-naphthalene-sulfonic acid (FD+C Yellow No. 6); 9-(o-carboxyphen0yl)-6-hydroxy-2,4,5,7-tetraiodo-3H-xanthen-3-one, disodium salt, monohydrate (FD+C Red No. 3); 2-(1,3-dihydro-3-oxo-5-sulfo-2H-indol-2-ylidene)-2,3-dihydro-3-oxo-1H-indole-5-sulfonic acid disodium salt (FD+C Blue No. 2); and [phthalocyaninato (2xe2x88x92)] copper.
Other compositions contemplated by the present invention are exemplified by U.S. Pat. Nos. 5,624,669; 5,582,834; 5,575,997; 5,514,371; 5,514,372; and 5,259,835; and U.S. patent application Ser. No. 08/714,288, the disclosures of all of which are hereby incorporated in their entirety by reference.

Sterilized cyanoacrylate solutions containing thickeners


Thermosensitive recording materials such as thermal paper with a thermochromic composition applied to the back thereof and overcoated with a protective coating provide a security feature without pre-reacting the active compounds in the thermosensitive recording materials or causing the loss of the color-forming properties of the thermosensitive recording materials. Methods for preparing thermal papers with a thermochromic composition as a security feature apply a thermochromic printing ink to the opposite side of the thermosensitive layer of the thermal paper followed by a coating composition that forms a protective coating over the thermochromic ink. The thermochromic printing ink and coating composition are selected so as not to pre-react with the thermosensitive layer or cause the loss of the color-forming properties of the thermosensitive layer.

The present invention relates to security inks used to thwart counterfeiting of printed commercial documents such as sales transaction records and receipts. More particularly, the invention relates to the use of security features on thermosensitive recording materials such as thermal paper.
Thermosensitive recording materials provide for the generation of print or designs without an ink ribbon by the application of heat energy thereto. Thermal paper is a typical example of a thermosensitive recording medium and typically comprises a base sheet, a base coating and a thermosensitive coating. Special color forming chemicals and additives are present in the thermosensitive coatings such that when heat is applied by a thermal head, the color forming chemicals react to develop the desired print or image.
The most common type of thermosensitive coating is the dye-developing type. There are three main color producing components in a dye developing-type thermal paper which are: a colorless dye (color former), a bisphenol or an acidic material (color developer) and a sensitizer. These solid materials are reduced to very small particles by grinding and incorporated into a coating formulation along with any optional additives such as pigments, binders and lubricants. This coating formulation is then applied to the surface of paper, typically a base sheet and base coating, or other support system using one of the various types of conventional coating application methods and dried. Images are formed on the coated surfaces by the application of heat to melt and interact the three color producing materials.
The use of special inks as a security measure, such as optically variable inks which change color when exposed to a light source other than ambient light and inks which provide latent images, is well known. Optically variable inks include fluorescent compounds which respond to infrared or ultraviolet light. Examples of printing inks which fluoresce under ultraviolet radiation, such as fluorescein, are described in U.S. Pat. Nos. 4,153,593; 4,328,332 and 4,150,997. Thermochromic compounds which change color at different temperatures is another type of optically variable ink. Examples of thermochromic compounds, also referred to as heat activatable chromogenic compounds, are described in U.S. Pat. Nos. 4,425,161; 5,427,415; 5,500,040; 5,583,223; 5,595,955; 5,690,857; 5,826,915; 6,048,347; and 6,060,428. Near-infrared fluorescent (NIRF) compounds provide another form of latent image as a means of security by reflecting radiation in the near-infrared range. Examples of NIRF compounds are described in U.S. Pat. No. 5,292,855, issued Mar. 8, 1994, U.S. Pat. No. 5,423,432 issued Jan. 13, 1995, and U.S. Pat. No. 5,336,714, issued Aug. 9, 1994. To be useful as a security measure on printed commercial documents, latent images must be well camouflaged but readily and easily viewable to the user. Preferably, this is accomplished by a simple procedure, particularly where records are only casually inspected, such as sales receipts and transaction records.
Where security features are desired from special compounds for thermal paper, these compounds must not pre-react the reactive components within the therrnosensitive coating of the thermal paper or prevent the formation of an image on the thermal paper from thermal printing. This will detract from the thermal paper""s printing performance. Certain chemical factors can adversely affect and degrade the performance of the thermosensitive coating and should be avoided such as some organic solvents (ketones), plasticizers (polyethylene glycol type), amines (ammonia) and certain oils (soy oil). The use of fluorescent compounds as a security feature for thermosensitive recording materials is described in U.S. Pat. No. 5,883,043. The use of NIRF compounds as a security feature for thermosensitive recording materials is described in U.S. Pat. No. 6,060,426, assigned to the same assignee as the present invention. While techniques for using fluorescent compounds and NIRF compounds as security features for thermosensitive recording materials have been effective, with the ease of counterfeiting made possible through the advent of today""s personal computers and color copiers, it is desirable to provide additional and alternative means of security, such as through the use of thermochromic compounds.
To protect thermal paper from environmental conditions, and premature coloration from handling, a number of developments have been made. One is to produce a barrier or protection layer on top of the thermal coating (see U.S. Pat. Nos. 4,370,370; 4,388,362; 4,424,245; 4,444,819; 4,507,669; and 4,551,738). Another approach is to encapsulate the reactive components in microcapsules which rupture or are permeable when exposed to heat. See U.S. Pat. Nos. 4,682,194; 4,722,921; 4,742,043; 4,783,493; and 4,942,150. These protective measures do not always prevent premature coloration of the thermosensitive coating.
U.S. Pat. No. 5,595,955 discloses coating a latent image comprised of a thermochromic ink, referred to therein as a xe2x80x9creversible thermosensitive recording material,xe2x80x9d printed on a support with a thin protective layer.
The present invention provides a thermosensitive recording material such as thermal paper with a thermochromic compound as a security feature printed on the side opposite the thermosensitive layer to prevent counterfeiting. The thermochromic compound is overcoated with a protective coating, preferably UV cured, so as not to pre-react the reactive components of said thermosensitive coating or cause the loss of the color-forming properties of the thermosensitive coating.
The thermochromic compound is shielded from reaction with the reactive components of the thermosensitive coating by a protective coating. This protective coating can be a UV cured coating or an air dried flexographic or lithographic coating. Such shielding preserves the activity of the thermochromic compounds and also the activity of the thermosensitive coating of the thermal paper so that it will still generate color when exposed to heat.
The thermochromic compounds provide a unique mode of security through their change in color in response to heat. Printed images which contain thermochromic compounds and another optically variable compound, such as a fluorescent compound, provide two modes of security.
The present invention also provides a method for preparing a thermosensitive recording medium having a thermochromic compound incorporated therein as a security feature without premature coloration of the thermosensitive layer. This method comprises printing a mark or image on the side of the thermosensitive recording medium opposite the thermosensitive coating using a thermochromic compound and overcoating the thermochromic compound with a protective coating, preferably a UV curable protective coating. The protective coating can be applied by conventional coating processes, such as flexography and lithography, and where necessary, cured. Conventional UV curing techniques can be used where appropriate.
The thermosensitive recording media of the present invention have a base sheet with a thermosensitive coating. Optionally, a conventional base coating is positioned between the thermosensitive coating and the base sheet. The base coating is typically comprised of inert pigments and binders and provides a smooth surface for the thermosensitive coating. This thermosensitive coating is preferably of the dye-developing type. Particularly suitable dye developer systems are those wherein the reactive dyes are colorless or white-colored which become dark colored when melted and exposed to a color developer. Such dyes are typically basic substances which become colored when oxidized by acidic compounds or bisphenol compounds. In these dye-developer systems, sensitizers are typically mixed with the dyes to form a blend with a reduced melting point. This reduces the amount of heat necessary to melt the dye and obtain reaction with the color developer. The components of the thermosensitive coating are often determined by the operating temperature of the thermal printer to be used. The operating temperature of conventional thermal printers varies widely, typically within the range of from 50xc2x0 C. to 250xc2x0 C. One skilled in the art can readily determine the melting point necessary for a desired application and select a dye and developer accordingly, or select a conventional thermal paper with a thermosensitive coating on one side. A well-known dye is that identified in the art as xe2x80x9cODB-II.xe2x80x9d A preferred color developer is bisphenol A and a preferred sensitizer is M-terphenyl.
Color formers suitable for use in the coating formulations in thermosensitive recording materials of this invention are leuco dyes. Leuco dyes are colorless or light-colored basic substances, which become colored when oxidized by acidic substances. Examples of leuco dyes that can be used herein are leuco bases of triphenylmethane dyes represented by formula I in U.S. Pat. No. 5,741,592. Specific examples of such dyes are: 3,3-bis(p-dimethylaminophenyl)-phthalide, 3,3-bis(p-dimethylaminophenyl)-6-dimethylaminophthalide (Crystal Violet Lactone), 3,3-bis(p-dimethylaminophenyl)-6-diethylaminophthalide, 3,3-bis(p-dimethylaminophenyl)-6-chlorophthalide, and 3,3-bis(p-dibutylaminophenyl)-phthalide.
Leuco bases of fluoran dyes represented by formula II in U.S. Pat. No. 5,741,592, are also suitable. Some examples of these fluoran dyes are: 3-cyclohexylamino-6-chlorofluoran, 3-(N-N-diethylamino)-5-methyl-7-(N,N-Dibenzylamino)fluoran, 3-dimethylamino-5,7-dimethylfluoran and 3-diethylamino-7-methylfluoran. Other suitable fluoran dyes include: 3-diethylamino-6-methyl-7-chlorofluoran, 3-pyrrolidino-6-methyl-7-anilinofluoran, and 2-[3,6-bis(diethylamino)-9-(0-chloroanilino)xanthylbenzoic acid lactam].
Also suitable are lactone compounds represented by formula III in U.S. Pat. No. 5,741,592 and the following compounds: 3-(2xe2x80x2-hydroxy-4xe2x80x2-dimethylaminophenyl)-3-(2xe2x80x2[-methoxy-5xe2x80x2-chlorophenyl)phthalide, 3-(2xe2x80x2-hydroxy-4xe2x80x2-dimethylaminophenyl)-3-(2xe2x80x2-methoxy-5xe2x80x2-nitrophenyl-phthalide, 3-(2xe2x80x2-hydroxy-4xe2x80x2-diethylaminophenyl)-3-(2xe2x80x2-methoxy-5xe2x80x2-methylphenyl)phthalide, and 3-(2xe2x80x2-methoxy-4xe2x80x2-dimethylaminophenyl)-3-(2xe2x80x2-hydroxy-4xe2x80x2-chloro-5xe2x80x2-methylphenyl)-phthalide.
There are many substances which change the color of the dyes by oxidizing them and function as developers. Color developers suitable for the coating formulations and thermosensitive recording materials of this invention are phenol compounds, organic acids or metal salts thereof and hydroxybenzoic acid esters.
Preferred color developers are phenol compounds and organic acids which melt at about 50xc2x0 C. to 250xc2x0 C. and are sparingly soluble in water. Examples of suitable phenol compounds include 4,4xe2x80x2-isopropylene-diphenol (bisphenol A), p-tert-butylphenol, 2-4-dinitrophenol, 3,4-dichlorophenol, p-phenylphenol, 4,4-cyclohexylidenediphenol 2,2-bis(4xe2x80x2-hydroxyphenyl)-n-heptane and 4,4xe2x80x2-cyclohexylidene phenol. Useful examples of organic acid and metal salts thereof include 3-tert-butylsalicylic acid, 3,5-tert-butylsalicylic acid, 5-a-methylbenzylsalicylic acid and salts thereof of zinc, lead, aluminum, magnesium or nickel.
Sensitizers or thermosensitivity promoter agents are preferably used in the thermal papers of the present invention to give a good color density. The exact mechanism by which the sensitizer helps in the color forming reaction is not well known. It is generally believed that the sensitizer forms a eutectic compound with one or both of the color forming compounds. This brings down the melting point of these compounds and thus helps the color forming reaction take place at a considerably lower temperature. Some of the common sensitizers which are suitable are fatty acid amide compounds such as acetamide, stearic acid amide, linolenic acid amide, lauric acid amide, myristic acid amide, methylol compounds or the above mentioned fatty acid amides such as methylene-bis(stearamide), and ethylene-bis(stearamide), and compounds of p-hydroxybenzoic acid esters such as methyl p-hydroxybenzoate, n-propyl p-hydroxybenzoate, isopropyl p-hydroxybenzoate, benzyl p-hydroxybenzoate.
Conventional base sheets and base coatings suitable for use in thermosensitive recording media can be used in the papers of the present invention. The base sheet or base coating must not contain any reactive elements which would prematurely color the thermosensitive coating or cause the loss of the color-forming properties of the thermosensitive coating. The thermosensitive coating can vary in composition, as is conventionally known in the art, including the encapsulation of components therein and the use of protective layers thereon to prevent premature coloration during handling. The thermosensitive coatings can also be applied by conventional methods using conventional equipment.
The thermochromic compounds employed in the thermosensitive recording media and methods of the present invention are selected to provide a security measure that is responsive to temperatures above ambient temperature (above 20xc2x0 C.) and below the temperature of activation for the thermosensitive recording media (typically about 60xc2x0 C.). One class of preferred thermochromic compounds are active at temperatures in the range of 21xc2x0 C. to 40xc2x0 C., (about 70xc2x0 F.-100xc2x0 F.). The compounds may be responsive to temperatures above this range but heating the thermosensitive recording media to temperatures above this range will activate most conventional thermosensitive layers. The thermochromic compounds are preferably stable to air, sun light and fluorescent light. When a flexographic process is employed to deposit the thermochromic compounds, these compounds are also preferably soluble, dispersible or emulsifiable in water to provide, xe2x80x9cwater basedxe2x80x9d formulations or inks. When a lithographic process is employed to deposit the thermochromic compounds, these compounds can be used in a hydrophobic or oil based formulation or ink. Water-based formulations are preferred to avoid the use of solvents that may pre-react the thermosensitive layer or cause the loss of the color-forming properties of the thermosensitive layer. The thermochromic compounds need not absorb or transmit visible light under ambient indoor conditions or when illuminated by light with wavelengths outside of the visible range. Preferred thermochromic compounds, have excellent thermal stability and little light absorption in the visible light region, i.e., they impart little or no color to the coatings and substrates to which they are applied. Preferably, they are transparent or invisible to the naked human eye under ambient light at ambient temperature (about 20xc2x0 C.).
Suitable thermochromic compositions include those described in U.S. Pat. Nos. 5,292,855; 5,423,432; 5,336,714; 5,461,136; 5,397,819; 5,703,229; 5,614,088; 5,665,151; 5,503,904; 4,425,161; 5,427,415; 5,500,040; 5,583,223; 5,595,955; 5,690,857; 5,826,915; 6,048,347 and 6,060,428. These include the conventional electron donor/electron-accepting combinations known in the art. Examples of electron donor compounds are described in U.S. Pat. No. 4,425,161 and include diarylphathalides, such as crystal violet lactone, polyarylcarbinols, leucoauramines, Rhodamine B lactams, indolines, spiropyrans and fluorans. Examples of electron-acceptor compounds are also described in U.S. Pat. No. 4,425,161 and include triazol compounds, thioureas, phenols, phenol resins, benzolthiozols, carboxylic acids, and metal salts thereof and phosphorous esters and metal salts thereof.
The thermochromic compositions typically also include one or more xe2x80x9csensitizersxe2x80x9d which can control the temperature at which color change occurs. Examples of sensitizer compounds include ketones, carboxylic acids, acid amides, hydrazides, alcohols, esters and phenols. Preferred thermochromic compositions are microencapsulated. Such microcapsules can be dispersed in a slurry, preferably a neutral aqueous slurry or can be dried to a dried powder. The encapsulant can vary widely in composition and include epoxy resins and polyurea resins. Microencapsulation can be performed by any conventional microencapsulation technique such as interfacial polymerization as described in U.S. Pat. Nos. 3,429,827 and 3,167,602, in situ polymerization as described in British Patent No. 989264, coacervation from an aqueous solution system as described in U.S. Pat. Nos. 2,800,457 and 3,116,206, a suspension coating method as described in U.S. Pat. No. 3,202,533, spray drying as described in U.S. Pat. No. 3,016,308 and the like. The microcapsules can be of a conventional size which are typically about 30 microns or less.
Encapsulated thermochromic compositions are preferably employed as printing ink formulations which comprise from about 1% by weight to about 50% by weight of the encapsulated thermochromic material. Preferred levels range from about 5% by weight to about 40% by weight of the microencapsulated thermochromic composition, based on the total weight of the printing ink.
These thermochromic printing inks may optionally contain a binder for the thermochromic composition or microencapsulated thermochromic material which does not react with the reactive compounds of the thermosensitive coating. These can include polymers such as hydrocarbon resins, polyester resins, polyurethane resins, epoxy resins, melamine resins and others discussed below.
The thermochromic prinking inks containing a thermochromic composition can have a solids content which ranges widely such as from 1 to 95 wt. % of the inks which includes the thermochromic composition, the binder components and other additives. For flexographic printing, a solids levels preferred for conventional flexographic printers such as those provided by Wolverine and Mark Andy are suitable. Solids levels which are conventional for lithographic inks are suitable when applying the thermochromic compound by lithographic printing.
The vehicle used in the thermochromic printing ink preferably dries by evaporation at a temperature below 50xc2x0 C. and most preferably is aqueous based. Vehicles based on organic solvents can be used if they do not pre-react the thermosensitive layer or cause the loss of the color-forming properties of the thermosensitive layer. Vehicles which dry by gelation, polymerization or solidification are also suitable.
The thermochromic printing inks preferably comprise an aqueous-based carrier so as not to pre-activate the thermosensitive layer or cause the loss of the color-forming properties of the thermosensitive layer. The carrier or vehicle can comprise an aqueous solution with or without a water soluble, dispersible or emulsifiable organic solvent which does not activate the thermal paper. The aqueous-based carrier may contain a dispersing agent to help solubilize the thermochromic compounds within the ink.
The thermochromic printing ink is preferably dried on the thermal paper by the evaporation of water and/or other volatile solvents/components within the ink to leave a solid layer. The binder compounds of the carrier and the amount thereof can vary widely, depending on the method intended to be employed for depositing the security ink on the base layer. For example, the amount of carrier, e.g. water, used can vary from 15 to 70 wt. % based on the total weight of the thermochromic printing ink.
The thermochromic composition and vehicle employed will depend on the printing equipment to be used. Thermochromic inks used in jet printing cannot contain large pigment particles or other solids in that they will clog the small orifices of the jet. The vehicle must also dry rapidly as well. Coating formulations applied by flexographic printing, gravure, wet-offset printing, lithography and relief printing, do not suffer from such limitations and can contain pigments of a relatively large particle size.
Preferably, a special apparatus is not needed to detect the presence of the thermochromic composition and simply rubbing the image or mark with a finger will generate a color shift. Devices which will excite the thermochromic composition include incandescent light sources, hot air dryers, resistance heaters, and other radiant energy sources which emit heat or infrared radiation. Preferred heat sources are those which can heat the surface of the thermosensitive compound to a temperature above ambient temperature but less than the temperature of activation of the thermosensitive layer, i.e., about 21xc2x0 C. to 51xc2x0 C.
The thermochromic compound typically has a defined temperature range at which the color shift is actuated. For example, thermochromic inks with actuator temperatures in the following ranges are commercially available from SICPA:
1xc2x0 C. to 12xc2x0 C. (33.8xc2x0 F. to 53.6xc2x0 F.)
22xc2x0 C. to 31xc2x0 C. (71.6xc2x0 F. to 87.8xc2x0 F.)
24xc2x0 C. to 33xc2x0 C. (75.2xc2x0 F. to 91.4xc2x0 F.)
27xc2x0 C. to 36xc2x0 C. (80.6xc2x0 F. to 96.8xc2x0 F.) and
32xc2x0 C. to 41xc2x0 C. (89.6xc2x0 F. to 105.8xc2x0 F.).
The thermochromic printing ink may contain additives such as resin binders discussed below, as well as pH stabilizers, UV stabilizers, surfactants, colored pigments, defoamers and plasticizers. The nature of these additives will depend on the end use.
The thermochromic print inks used on the thermosensitive recording media of this invention may comprise a thermoplastic resin binder component. Thermoplastic resins suitable as binders include polyvinyl chloride, polyvinyl acetate, vinyl chloride-vinyl acetate copolymers, polyethylene, polypropylene, polyacetal, ethylene-vinyl acetate copolymer, ethylenealkyl(meth)acrylate copolymer, ethylene-ethylacetate copolymer, polystyrene, styrene copolymers, polyamide, ethylcellulose, epoxy resin, polyketone resin, polyurethane resin, polyvinylbutryl, styrenebutadiene rubber, nitrile rubber, acrylic rubber, ethylene-propylene rubber, ethylene alkyl(meth)acrylate copolymer, styrene-alkyl(meth)acrylate copolymer, acrylic acid-ethylene-vinylacetate terpolymer, saturated polyesters and sucrose benzoate. To obtain emulsions of polymers which are insoluble or partially soluble in water, the resin is typically ground to submicron size.
Thermosensitive recording media which contain a thermochromic security feature can be prepared by printing a mark or image with a thermochromic printing ink having a thermochromic composition therein on the side opposite the thermosensitive coating using conventional printing equipment. The printing operation preferably does not require temperatures above 125xc2x0 F. (51xc2x0 C.). Examples include relief printing, flexography, wet-offset, lithography and gravure. Flexographic printing and lithographic printing are preferred, particulary where other indicia are printed on the thermal paper by the same technique, i.e., either flexographic or lithographic printing. Where the thermochromic printing ink is applied to a base sheet of a thermal paper prior to application of the thermosensitive layer, the printing operation/procedure is not limited by temperature. Where the thermochromic printing ink is applied after application of the thermosensitive coating, only methods which do not require elevated temperatures, above 125xc2x0 F. (51xc2x0 C.) can be used. Once the thermochromic printing ink is applied to a base sheet with a thermosensitive coating, it is dried at temperatures preferably less than 51xc2x0 C., most preferably at ambient temperature. Suitable commercially available thermochromic printing inks active at temperatures in the range of 21xc2x0-51xc2x0 C. include: 744020TC (thermochromic blue), 744010TC (thermochromic turquoise), 744027TC (thermochromic yellow), 734010TC (thermochromic rose), 724010TC (thermochromic orange), 754027TC (thermochromic green) sold by SICPA Securink Corp. Springfield, Va. Included are the thermochromic inks which lose color when heated, i.e., change from a color to clear. This includes the compounds 138000TC5 (rose/clear) and 178002TC (Blue/clear) available from SICPA Securink Corp. which are active at 1xc2x0 C.-12xc2x0 C. Marks and images made of these compounds are colorless at ambient temperature and change color when cooled. The compound 178002TC (Black/clear) from SICPA Securink Corp. is active at 27xc2x0 C.-36xc2x0 C. Compounds from SICPA Securink Corp. which are active at 22xc2x0 C.-31xc2x0 C. include: 128001TC (orange/clear), 1384175TC (rose/clear), 150015TC (green/clear), 148003TC (blue/clear), 178000TC (black/clear), 14001TCBR (blue/red) and 128001TCY (orange/yellow). Compounds from SICPA Securink Corp. which are active at 24xc2x0 C.-33xc2x0 C. include: 118000TC (yellow/clear), 128002TC (orange/clear), 138103TC (vermillion/clear), 15002TC (green/clear), 14001TC (blue/clear), 14000TCBR (blue/red) and 128002TC (orange/yellow). Compounds from SICPA Securink Corp. which are active at 32xc2x0 C.-41xc2x0 C. include: 13001TC (rose/clear), 148002TC (blue/clear), 178001TC(black/clear) and 178002TCBR(blue/red).
To provide the thermochromic printing ink, the components are typically combined as dispersions at about 30 wt. % solids in a ball mill or similar conventional grinding equipment and agitated and ground, without rupturing the microcapsules. Where a resin emulsion is used, it is typically the initial material and the remaining components are added thereto with minor heating. Fluorescent inks may be added to provide another mode of security.
The thermochromic mark or image printed on the reverse side of the thermosensitive recording medium is overcoated with a protective coating so as not to insulate the thermochromic mark or image from heat. The coating preferably has a thickness of from 0.05 to 2.0 mils. It should be recognized that higher thicknesses will not affect the chemical activity of the thermosensitive coating for the thermosensitive recording media. However, the thermochromic mark or image will be more difficult to activate with thicker protective coatings because of the insulation effect.
The overcoat is preferably applied by the same printing method employed to print the thermochromic mark or image with the thermochromic ink. Flexographic and lithographic printing methods are preferred for both applying the thermochromic printing ink and the protective overcoat. The overcoat can vary significantly in composition from a UV cured polymer coat to a heat cured polymer coating cured at temperatures of up to 120xc2x0 F. to a condensed polymer coating where the ink air dries. This overcoating serves to protect these thermochromic composition from interacting with the thermosensitive layer of the thermosensitive recording medium when stored on a roll.
Conventional coatings deposited over the thermosensitive layer of the thermosensitive recording medium can be used as a protective layers for the thermochromic mark or image. Examples include acrylate coatings, varnishes, polyvinyl alcohol coatings, polyvinyl chloride coatings, styrenated layers and styrenated maleic anhydride layers as described in U.S. Pat. No. 5,843,864 and cellulose binders with a synthetic wax, as described in U.S. Pat. No. 4,740,495.
Suitable UV cured protective overcoats are described in U.S. Pat. No. 4,886,744. Most free radical initiated polymerizations can be suitably cured with the use of a photoinitiator that is responsive in the UV range. These UV overcoats are said to contain additives such as UV absorbers and light stabilizers. Employing the UV cured coating allows for rapid drying. U.S. Pat. No. 4,886,774 discloses the use of a coating comprising the reaction product of acrylated aromatic urethane oligomers as unsaturated oligomer, tetrahydrofural methacrylate, as methacrylate oligomer and trimethylolpropane triacrylate as crosslinking monomer. U.S. Pat. No. 5,158,924 also describes ultraviolet curing resins which are suitable for protective coatings and include urethane resins, epoxy resins, organosiloxane resins, polyfunctional acrylate resins, melamine resins, thermoplastic resins having high softening points such as fluorine plastics, silicone resins, and polycarbonate resins. A specific example of a urethane acrylate-type UV curing resin is UNIDIC C7-157 made by Dainippon Ink and Chemicals Incorporated.
The entire disclosure of all applications, patents, publications, cited above and below, are herein incorporated by reference.
Thermal Paper
Commercially available thermal papers consisting of substrate paper, base coat and active (thermosensitive) coat are used.
The base coat (40% solids) comprises conventional base coat components such as pigments/binders to produce a level surface for the thermosensitive coat coating.
The active coat comprises conventional active coat components such as the dye ODB-2, a bisphenol-A coreactant, a sensitizer and a stabilizer.
The Thermochromic Printing Ink
The thermochromic printing ink used is water-based and sold by SIPCA Securink Corp. of Springfield, Va. The ink responds with color changes at temperatures in the range of 21xc2x0 C. to 41xc2x0 C. This thermochromic printing ink is printed on the side of paper (5) opposite the thermosensitive layer, as shown in FIG. 1 and described above using a Mark Andy 830 Flexopress. The ink printed forms a transparent image, such as image (10) of FIG. 1, which is the NCR Corporation logo.
Protective Coating
An acrylate overcoat (30) is formed over the thermochromic compound by applying a UV curable acrylate coating over the NCR logo with a Mark Andy 830 flexopress and exposing the coating to a UV lamp.
Security Test
Portions of the xe2x80x9cNCRxe2x80x9d logo or the complete logo are detected as pink markings (20) both during and after the press run with the application of heat by rubbing the image with a finger.
A lithographic ink is printed on a thermal paper as described in Example 1 on the side opposite the thermosensitive layer. The lithographic ink is a conventional oil-based ink with conventional thermochromic compounds, an example of which changes color at temperatures in the range of 21xc2x0 C. to 41xc2x0 C. This lithographic ink is printed on the thermal paper as described above using a conventional lithopress. The ink printed forms a transparent image as in Example 1. A varnish is applied over the transparent image, also by a lithographic press, forming an overcoat above this image. Portions of the image (or the complete image) are detected with the application of heat by rubbing the image with a finger.


A lip care moisturizing product in the form of a water-in-oil emulsion, containing at least one fatty acid ester, at least one wax, the total of said at least one fatty acid ester and said at least one wax being at least about 1.0%, liposomes containing water therein, and an emulsifier. The emulsifier is preferably a mixture of behenoyl stearate and sodium borate, and the liposomes preferably contain a mixture of water and glycerin.

The invention relates to the field of lip care products, including lipsticks and lip balms with penetrating ingredients.
Lipsticks have been used for many years to alter appearance of the lips and the facial characteristics of the wearer. For example, narrow lips may be widened and broad lips narrowed. Besides altering the shape of the lips, lipsticks can be made in a great number of colors and shades according to fashion and the mood of the wearer.
Lipsticks are most often based on waxy and oily materials, which give the lips an oily and shining look, but a greasy feel. Among such lipophilic materials are hydrocarbon oils, fatty acid esters, waxes, fatty alcohols and mixtures thereof. Lipsticks may also contain other emollients which provide a supple and pleasant feeling to the lips of the wearer. It has also been proposed to include a small amount of water in some lipsticks for moisturizing the lips, the water being emulsified in the waxy material by the use of various emulsifiers and polymers. However, water containing lipsticks have been found to be deficient in terms of storage stability; in particular, with a semi-open package, it is difficult to retain the moisture intact. Moreover, the water content of such products has often been undetectable to the user. Thus, female consumers still favor anhydrous colored lipsticks.
Lip balms are similar to lipsticks and have long been used to protect lips from the effects of the environment, such as sunlight, wind, and cold. Lip balms are generally occlusive compositions which may contain a variety of lipophilic materials such as fats, oils, waxes and emollients which soften lips and protect against the effects of wind. Both lipsticks and lip balms may contain sunscreens which block damaging radiation from the sun and other ingredients for imparting fragrance, and physical characteristics.
It is therefore an object of the invention to provide a lip moisturizing product with a stable water content over time.
It is a further object of the invention to provide a lip moisturizing product containing moisturizers which penetrate into the skin.
To achieve these and other objects, the invention is directed to a lip care moisturizing product in the form of a water in oil emulsion in which the water content is in the form of liposomes containing water and glycerin, the liposomes being dispersed in the oily/waxy phase by an emulsifier system preferably based on behenoyl stearate and sodium borate (borax).
As used herein the term xe2x80x9clip care moisturizing productxe2x80x9d refers to lipsticks, lip balms, and other products used to treat the lips whether in solid or pasty form. The lip care products of the invention are based on the use of liposomes, which are defined generally as spherical, closed bilayer structures formed by hydrating lipids or lipid-like amphiphilic materials under appropriate conditions. Liposomes may be differentiated based on lamellarity, size, and function. Small unilamellar vesicles (SUV""s) have a size between 25 and 75 nm, while large unilamellar vesicles (LUV""s) have a size greater than 100 nm. Unilamellar liposomes that are stearically stabilized by incorporating proteins are known as xe2x80x9cstealth liposomesxe2x80x9d while liposomes containing cationic lipids carry a net positive charge and are known as cationic liposomes. Liposomes may also contain lipids designed to bind to specific cells or proteins, and these are known as targeted liposomes.
Various methods are known for producing liposomes.
In a first method, a solution of lipid is dried in a high vacuum to remove all organic solvent, then hydrated in an appropriate buffer to produce a raw liposome dispersion, which is generally a mixture of univesicular and unilamellar liposomes. The dispersion can be forced through a membrane to obtain large unilamellar vesicles, with size depending on the pore size of the membrane. Alternatively, the raw dispersion can be treated by sonication to obtain small unilamellar vesicles, which are harvested by ultracentrifugation.
A mixture of large and small unilamellar liposomes can be prepared by dissolving dry lipids in aqueous media in the presence of a detergent, then removing the detergent by dialysis.
Industrially, liposomes can be obtained by forming a slurry of lipid in water and microfluidizing at 12,000-14,000 PSI. This process can be performed continuously to produce unilamellar liposomes and no organic solvent is necessary.
A particularly preferred liposome for the products of the invention is sold as Liposomes FG(trademark) by The Collaborative Group, Ltd. of East Setauket, N.Y. These liposomes are formed of lecithin as the lipid and contain a mixture of water and glycerin.
The compositions of the invention comprise a stable emulsion base containing about 1.0 to 35.0% by weight purified water, and about 0.2% to 30% by weight liposome dispersion containing a purified water-glycerin mixture. In one embodiment, the liposome dispersion contains 82% by weight liposomes and 18% by weight of a water-glycerin mixture. The liposomes are preferably in the size range of about 25 to 75 nm.
The emulsion base also preferably contains 0.05 to 20% by weight, and preferably less than 5% by weight, of a gelling agent, i.e. cholestryl/behenyl/octyldodecyl lauroyl glutamate, which will absorb and retain water in an amount of 4% to 300% of its own weight.
The compositions of the invention typically contain a mixture of esters and waxes as the base material, although the particular esters and waxes used are not critical. Typical esters used in such products include jojoba esters, dioctyl adipate, octyl stearate, octyl palmitate and caprylic/capric triglycerides. Esters are typically present in a total amount of about 0.5 to 35% by weight, preferably about 5 to 35% by weight.
Typical waxes used are ozokerite (ceresin), microcrystalline waxes and petrolatum, in a total amount of about 0.5 to 29% by weight, preferably about 3 to 29% by weight.
The total amount of esters and waxes will affect the physical form of the product. Thus, pasty products will generally have between about 1 and 25% by weight total esters and waxes, whereas solid products like lipsticks and lip balms will generally have between about 5 and 35% by weight total esters and waxes.
Sunscreens which may be used include octylmethoxycinnamate and benzophenone-3, in amounts necessary to achieve sun protection factor (SPF) 15. The total amount of sunscreen in the composition is generally in the range of 5.0 to 30% by weight, preferably 7.0 to 15% by weight.
The compositions preferably contain one or more penetrating moisturizers, particularly squalane and panthenol in a total amount of about 0.5 to 5% by weight.
The water in oil emulsions of the invention are typically produced using stearate emulsifiers, for example glyceryl stearate, PEG stearate and behenoyl stearate. Behenoyl stearate emulsifier is very effective in emulsifying 33-55% by weight water into 45-67% by weight of non-polar oils. The best results are obtained by dissolving about 2-7.5% by weight emulsifier in the oil phase, and buffering the system by dissolving up to 4% by weight borax in the water phase.
A typical composition according to the invention thus contains, by weight:
A preferred composition also contains a skin protectant, and has the following composition, by weight:
The composition is prepared by mixing the waxes and esters and melting together to form an oil phase. The purified water is blended with cholestryl/behenyl/octyldodecyl lauroyl glutamate and passed through a high shear inline micronizer to form a water phase. The oil phase and the water phase are mixed together and passed through a high shear micronizer to obtain a water in oil emulsion. Pre-blending of the water phase is important to stabilize the emulsion without loss of moisture during further processing.
After obtaining the emulsion, liposomes are purged into the system at a rate of 1 liter per hour at a temperature below 45xc2x0 C. while mixing at less than 400 RPM. Because liposomes are delicate, excessive heat and shearing are to be avoided in the mixing step.